In this proposal, the outlined experiments aim at providing an integrated view of the oncolytic potential of Newcastle Disease Virus and the elicited host immune response as an important player in tumor therapy. As such, expression of a tumor associated antigen by rNDV will be explored as a means to enhance its antitumor properties through a more efficient stimulation of specific anti-tumor immune responses. In addition to its oncolytic properties, infection of tumor cells by NDV results in the immunostimulation of anti-tumor cellular responses, most likely due to the induction of cytokine and chemokine secretion by the infected cells. However, until recently, the use of NDV as an anti-tumor agent was restricted to naturally-occurring strains of the virus. We hypothesize that a rNDV expressing a tumor associated antigen will induce an increased antitumor immune response leading to an enhanced stimulation of tumor specific CTLs and tumor regression. The goals of the studies proposed here are highly relevant to the understanding of the cancerous state at the immunological level, as the induction of the immune response by NDV can potentially be enhanced by eliciting specific anti-tumor immune responses, and can be a critical step in tumor therapy.